DESCRIPTION: The two genes, period (per) and timeless (tim) are involved in the specification of circadian rhythms in the fruit-fly, Drosophila melanogaster. Previous work has shown that proteins encoded by these two genes associate physically, and the complex thus created is important in controlling several aspects of the clock that functions to maintain behavioral and developmental cycles. This proposal has five specific aims; they involve further characterization of the protein expression pattern of tim, and its relation to the expression of per; determination of the molecular basis of light sensitivity of Tim and the regulation of co-localization of Tim and Per in cultured cells. The two remaining specific aims pertain to the identification of other genes that may play a role in the generation of circadian rhythms. To this end, proteins identified through two-hybrid interactions with Per will be followed up, and a new gene, doubletime, which can be mutated to yield flies with short rhythms, will be further characterized.